Efforts at improving myocardial protection during cardiac surgery and improved methods of long-term preservation of the heart have focused on changes in cardiac function and metabolism. Evaluation of different methods of protection has tended to be empiric. Studies of different types of myocardial injury have shown the importance of the microcirculation. Microvascular injury is common to many different types of cardiac insult and is responsible for the "no reflow" phenomenon and myocardial edema. The normal physiology of the myocardial microcirculaton has only recently begun to be understood. New techniques have been developed to study the microvasculature directly. These have enabled dired measurements of microvascular permeability by the indicator diffusion technique. Ultrastructural tracer methods have allowed study of the rate and mechanism of endothelial transport of different sized probes. Morphologic studies using intravascular tracers and histochemical techniques have allowed study of the proportion of capillaries being perfused and direct examination of endothelial injury as a result of ischemia and other insults. These methods of studying the microcirculation directly have not been systematically applied to the conditions which pertain during cardiac surgery and long-term preservation of the heart. We propose to use these methods to study both the functional and morphologic changes in the microvasculature during short- and long-term preservation of the heart. The importance of these changes in cardiac injury and recovery will be evaluated. In addition, new techniques of studying the microcirculation such as direct in vivo cinematography and the use of fluorescent tracers will be developed. The effects of cardiopulmonary bypass, ischemia, and reperfusion, hypothermia, cardioplegia, and long-term preservation of the isolated heart will be studied. Methods of modifying the changes in the microvasculature will be studied. Pharmacologic agents will be tested with direct measurements of their effect on the microcirculaton. It is hoped that study of microvascular injury will improve methods of preserving the heart on a rational basis.